Neuroendocrine lung cancer is one of the most common types of cancer in smokers but has never been induced in an animal. This project is based on the discovery that simultaneous exposure of hamsters to hyperoxia and diethylnitrosamine (DEN) induces a high incidence of neuroendocrine lung cancers while hyperoxia alone, or DEN alone lead to a pronounced increase of pulmonary endocrine cells. This unique in vivo model is of potentially great importance for studies into mechanisms of development of this poorly understood malignancy as well as chemopreventive and therapeutic investigations. However, a prerequisite for all such research is an in-depth characterization of the tumors. The specific aims of this project are: To study the pathology, neuroendocrinology and molecular biology of neuroendocrine lung tumors induced in Syrian golden hamsters by exposure to hyperoxia and DEN and to correlate pathological changes with alterations in neuroendocrine and genetic markers during tumor development.